Intravenous N-Acetylcysteine for the Treatment of Acute Ischemic Stroke

NCT04918719 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 32358-01
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Stroke is a major cause of death and long-term disability in the developed world. While t-PA and mechanical thrombectomy have been shown to decrease disability in properly selected patients, many patients are left with lifelong symptoms. There are currently limited options available for patients who are not candidates for treatment with t-PA and/or mechanical thrombectomy. N-Acetylcysteine (NAC) is an FDA approved antioxidant and anti-inflammatory agent that has been used safely for many years in the treatment of acetaminophen overdose. In studies, the oral form has been shown to improve outcomes in acute ischemic stroke and has been shown to decrease the effects of ischemic brain injury in animal models. In a small human trial, it improved outcomes in patients suffering from mild traumatic brain injury (TBI). The intravenous formulation has a long safety record. It is not FDA approved for treating stroke but was reviewed by the FDA and was given an FDA IND for this study. The investigators propose a prospective randomized, double-blind, placebo-controlled study to evaluate the efficacy of administering intravenous N-acetylcysteine to patients with acute ischemic stroke. Eligible subjects will receive a commercially available form of intravenous NAC (Acetadote®) through for the first 20 hours following their enrollment. Patients enrolled who receive t-PA for thrombolysis will have their intravenous NAC infusion delayed for 24 hours after the completion of their t-PA infusion. Patients undergoing thrombectomy will be excluded from enrollment. Subjects will be evaluated by emergency department and/or division of neurology physicians at the time of enrollment, during their hospitalization, as well as 30 days and 90 days after enrollment. At each visit, subjects will be assessed for functional status and quality of life. This study is designed to compare the efficacy of intravenous N-acetylcysteine compared to normal treatment in patients with acute ischemic stroke.

Conditions

Acute Ischemic Stroke

Keywords

non-hemorrhagic

Outcome Measures

Primary Outcomes (1)

• National Institutes of Health Stroke Scale (NIHSS)

  The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The single patient assessment requires less than 10 minutes to complete. The evaluation of stroke severity depends upon the ability of the observer to accurately and consistently assess the patient.

  From the time of enrollment until 90 days (looking at change in NIHSS)

Secondary Outcomes (5)

• Modified Rankin Scale for Neurologic Disability(MRS)

  Obtained at 90 days

• Glascow Outcome Scale (GOS)

  Obtained at 90 days

• Barthel Index (BI)

  Obtained at 90 days

• Neuronal specific enolase blood level

  From the time of enrollment and at 90 days

• MRI

  Comparison of the volume of stroke noted on initial MRI will be compared to MRI at 90 days

Study Arms (2)

NAC arm

EXPERIMENTAL

Both arms are subjects who present with neurological deficits consistent with stroke without hemorrhage less than 24 hours since symptom onset. Both arms will receive standard of care with the study intervention being considered an "add-on" therapy. Thirty minutes after enrollment, eligible subjects will be randomized into one of two arms: placebo or N-Acetylcysteine (NAC). Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion. The dosing of NAC will be similar to the standard intravenous acetaminophen toxicity dosing: 200mg/kg in 1 liter of 5% Dextrose (D5W) infused over 4 hour, then 100mg/kg in 1000 milliliters D5W infused over 16 hours

Drug: Acetylcysteine

Placebo arm

PLACEBO COMPARATOR

Both arms are subjects who present with neurological deficits consistent with stroke without hemorrhage less than 24 hours since symptom onset. Both arms will receive standard of care with the study intervention being considered an "add-on" therapy. Thirty minutes after enrollment, eligible subjects will be randomized into one of two arms: placebo or N-Acetylcysteine(NAC). Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion. The placebo will consist of a 5% Dextrose in Water (D5W) instead of NAC (dosage and timings are the same as the NAC arm).

Drug: Dextrose in Water

Interventions

Acetylcysteine DRUG

The dosing of Acetylcysteine will be similar to the standard intravenous acetaminophen toxicity dosing: 200mg/kg in 1 liter of 5% Dextrose (D5W) infused over 4 hour, then 100mg/kg in 1000 milliliters D5W infused over 16 hours (Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion. )

Also known as: N-acetylcysteine

NAC arm

Dextrose in Water DRUG

The placebo will consist of a 5% Dextrose in Water instead of NAC (dosage and timigs are the same as the NAC arm). (Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion. )

Also known as: D5W, 5% Dextrose in Water

Placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Consecutive subjects between ages 18 years or older evaluated in the emergency department at Harbor-UCLA Medical Center with signs and symptoms of acute ischemic stroke presenting within 24 hours of symptom onset. All individuals regardless of gender or race, who have an NIHSS of at least 5 will be eligible for this study to be included. For adults who cannot consent for themselves because of the severity of their stroke, one of the investigators will offer participation in the study to the family member who possesses the authority for medical decision making for the patient. There is no financial incentive for either the patient or the investigator. It will also be explained that the potential benefit of giving N-acetylcysteine is unknown and that the patient will receive excellent care (standard for their presentation) whether they participate or not and outside of not receiving the study drug.
• Our patients tend to be economically disadvantaged but since there are no financial incentives either for the patient or for the investigators, this bias has been minimized. Patients will receive the same care whether they participate in the study or decline.

You may not qualify if:

• Evidence of hemorrhagic stroke on initial CT scan
• Need for thrombectomy as determined by the treating neurologist -Known allergy to NAC
• Protected populations, including age \< 18, known pregnancy, and prisoners
• Patients who are DNR/DNI at the time of presentation with a short life expectancy

Sponsors & Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: lead

Study Sites (1)

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

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Related Links

• Foundation NS. Clinical Guidelines For Stroke Management. Melbourne Australia2010.

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Acetylcysteine; Glucose; Water

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Hexoses; Monosaccharides; Sugars; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• David Tanen, MD

  Lundquist LABiomed

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sylvia Youn, Pharm.D., the ED Pharmacist will maintain drug accountability logs in compliance with FDA regulations. She will instruct other ED pharmacists about the study and the randomization log which will be kept in the pharmacy room in the ED. She will also create study drug labels to keep the nurses, physicians and patients blinded to the study medication.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Residency Director & Senior Physician, Department of Emergency Medicine

Model Details: Randomized double blinded clinical trial

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: June 9, 2021
• Study Start: November 2, 2023
• Primary Completion: September 17, 2024
• Study Completion: September 17, 2024
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)